Some of the most debilitating diseases afflicting humans and other animals are either caused by insects or are vectored by them. Insect host- parasite relationships are integrating adaptations of considerable complexity. Little is known about the mechanism(s) insects use to recognize foreignness and to combat these infections. The long term goals of the proposed research are to identify the cytotoxic molecules produced by insect blood cells (hemocytes) during immune challenge, and to clarify the mechanisms by which these substances specifically target and destroy organisms that have invaded the body cavity of the host. The major focus of the proposed study concerns the involvement of hemocyte NADPH oxidase and inducible nitric oxide synthase (iNOS), since these enzymes are essential not only for the generation of cytotoxic reactive oxygen species by activated hemocytes, but also for intracellular and collaborative cell-cell signaling required for successful host encapsulation responses.